Background: Allogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable\ncellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening\ncomplications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs.\nAdoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We\nreport here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell\n(ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted\nwith umbilical cord blood (UCB).\nMethods: Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon\n(IFN)-Ã?³-based immunomagnetic isolation from a leukapheresis from their original donor (42.9%) or a third party\nhaploidentical donor (57.1%). One patient resolved ADV infection before infusion, and ADV-VST could not reach\nrelease or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral\ndrugs as a pre-emptive treatment.\nResults: One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST\n(mean 5.83 Ã?± 8.23 Ã?â?? 103 CD3+IFN-Ã?³+ cells/kg) up to 9 months after transplantation. The 11 patients showed in\nvivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of\nthe patients (91%). Neither de novo GVHD nor side effects were observed during the first month post-infusion,\nbut GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of\nthese patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during\nfollow-up, one due to refractory ADV disease.\nConclusions: Adoptive transfer of rapidly isolated ADV-VST is an effective therapeutic option for achieving in\nvivo expansion of specific T cells and clearance of viral load, even as a pre-emptive treatment. Our study\nhighlights that third party haploidentical donors are of great interest for ADV-VST generation in the context of\nUCB transplantation. (NÃ?° Clinical trial.gov: NCT02851576, retrospectively registered).
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